MOUSE STRAIN-DEPENDENT VARIATION IN THE COURSE AND OUTCOME OF CHLAMYDIAL GENITAL-TRACT INFECTION IS ASSOCIATED WITH DIFFERENCES IN HOST RESPONSE

Whether there is a pathogenic or protective outcome to chlamydial infe ction may be defined by the host response, We infected C57BL/6 (C57) a nd C3H/HeN (C3H) mice with the human biovar of Chlamydia trachomatis, serovar E, and, in select experiments, with the mouse pneumonitis agen t of C, trachomatis (MoPn), We compared the courses of infection, hist opathology, and host responses that resulted from these infections, Th e duration of infection with either chlamydial biovar was significantl y increased in the C3H strain of mice, The intensity of infection was examined in mice infected with serovar E, and it was significantly inc reased in the C3H strain, Histopathology revealed the incidence of sev ere hydrosalpinx to be significantly greater in C3H mice than in C57 m ice, In contrast, severe distention of the uterine horns was observed in all infected C57 mice compared to none of the C3H mice infected wit h serovar E and only 25% of those infected with MoPn. Acute inflammati on was significantly increased in the uterine horns of C57 mice compar ed to that of C3H mice, Examination of antigen-specific responses reve aled qualitatively similar responses in the two strains, Determination of gamma interferon- versus interleukin 4- producing cells revealed t he predominance of a Th1 response in both strains, Serum enzyme-linked immunosorbent assays for immunoglobulin G1 (IgG1) and IgG2a revealed a predominance of IgG2a antibody in both strains, although the levels of antibody were significantly greater in C3H mice, Lymphocyte prolife ration studies revealed increased proliferation in the iliac nodes of both strains at 1 to 3 weeks after infection, Because of the early era dication of infection observed in the C57 strain, we explored the rela tive production of tumor necrosis factor alpha (TNF-alpha) in the two strains, TNF-alpha levels were significantly increased in the genital tract secretions of C57 mice compared to that of C3H mice during the f irst week of infection, Increased TNF-alpha may be beneficial to the h ost by leading to earlier eradication of infection, thereby preventing infection of the oviduct and thus the major disease sequelae associat ed with chlamydial infection of the genital tract.